{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:21Z","timestamp":1787013981788,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["24ck0106972h0001"],"award-info":[{"award-number":["24ck0106972h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["Grant\u2010in\u2010Aid for Scientific Research (B) 20H03"],"award-info":[{"award-number":["Grant\u2010in\u2010Aid for Scientific Research (B) 20H03"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Mesothelioma is one of the most aggressive neoplasms worldwide that has a particularly poor prognosis. We have previously discovered that oxytocin receptors (OXTR) are highly expressed in mesothelioma and that\n                    <jats:italic>OXTR<\/jats:italic>\n                    knockdown significantly decreases the proliferation of mesothelioma cells with high\n                    <jats:italic>OXTR<\/jats:italic>\n                    expression. In this study, we performed quantitative proteomic profiling of two mesothelioma cell lines with high\n                    <jats:italic>OXTR<\/jats:italic>\n                    expression using mass spectrometry to investigate the downstream signals of OXTR in mesothelioma cells. We found that\n                    <jats:italic>OXTR<\/jats:italic>\n                    knockdown significantly downregulated PDZ\u2010binding kinase (PBK)\u2014a serine\/threonine protein kinase belonging to the bispecific MAPKK family.\n                    <jats:italic>PBK<\/jats:italic>\n                    knockdown significantly suppressed proliferation, migration, and colony formation in mesothelioma cells with high\n                    <jats:italic>PBK<\/jats:italic>\n                    expression and decreased Akt and MAPK phosphorylation levels. Furthermore, immunohistochemical analysis of PBK in surgical specimens obtained from patients with mesothelioma showed that high PBK expression was strongly associated with poor overall survival (log\u2010rank test\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0031; hazard ratio 3.339 and 95% confidence interval 1.12\u201310.00) and recurrence\u2010free survival (log\u2010rank test\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0024; hazard ratio 3.355 and 95% confidence interval 1.25\u20139.04). In addition, the clinical significance of PBK expression was validated in mesothelioma using datasets from TCGA. Multivariable Cox regression analysis, incorporating stage and\n                    <jats:italic>OXTR<\/jats:italic>\n                    mRNA expression, demonstrated that\n                    <jats:italic>PBK<\/jats:italic>\n                    mRNA expression was the strongest independent predictor of OS. Our findings indicate that PBK plays a crucial role in the aggressiveness of mesothelioma, making it a promising therapeutic target and potential prognostic biomarker for mesothelioma.\n                  <\/jats:p>","DOI":"10.1111\/cas.70124","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:59:52Z","timestamp":1750813192000},"page":"2413-2426","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>PBK<\/scp>\n                    Expression Promotes the Aggressive Phenotypes of Mesothelioma"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4789-7157","authenticated-orcid":false,"given":"Kazumi","family":"Hori","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine Nagoya University Graduate School of Medicine  Nagoya 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